1. Field of the Invention
The present invention relates to a process for preparing a derivative of azolylmethylcycloalkanol which is useful as an active ingredient of antifungal compositions.
2. Description of Background Art
As a process for preparing azolylmethylcycloalkanol derivatives, U.S. Pat. No. 4,938,792, for example, discloses a process comprising preparing a methylenecyclopentane derivative from a cyclopentanone derivative, epoxidizing the methylenecyclopentane derivative to produce an oxirane derivative, and reacting the oxirane derivative with an azole compound, according to the following reaction formula (a). ##STR2## wherein R.sup.11 and R.sup.21 respectively represent hydrogen atom or C.sub.1 -C.sub.5 alkyl group; X.sup.1 represents halogen atom, C.sub.1 -C.sub.5 alkyl group, or phenyl group; q represents an integer of 0 to 2; A represents nitrogen atom or CH group; and M.sup.11 represents hydrogen atom or alkali metal atom, provided that R.sup.11 is not hydrogen atom when R.sup.21 is hydrogen atom.
EP 329397 discloses a method for reacting a cyclopentanone derivative, sulfonium methylide or sulfoxonium methylide, and an alkali metal salt of azole compound or an azole compound and a base, in a polar solvent containing an amide bond or dimethylsulfoxide, or in a mixed solvent of this polar solvent and an alcohol, according to the following reaction formula (b); and a method for reacting a cyclopentanone derivative and an alkali metal salt of azole compound or an azole compound and a base, while intermittently adding trimethylsulfonium halide or trimethylsulfoxonium halide to a solution of these reactant compounds. ##STR3## wherein R.sup.12 represents hydrogen atom or C.sub.1 -C.sub.5 alkyl group; R.sup.22 represents hydrogen atom or C.sub.1 -C.sub.2 alkyl group; X.sup.2 represents halogen atom, C.sub.1 -C.sub.4 alkyl group, phenyl group, and the like; A represents nitrogen atom or CH group; M.sup.12 represents hydrogen atom or alkali metal atom; and r represents an integer of 1 to 5.
As a method for epoxidation of ketones or aldehydes, Tetrahedron Lett., 23, 5283-5286 (1982) describes that ketones (acetophenone, 2-acetylfurane, etc.) can be epoxidized by a solid-liquid two-phase reaction using trimethylsulfonium iodide, potassium hydroxide, acetonitrile, and a small amount of water. Further, Tetrahedron, 1985, 1259-1266 describes that benzalehyde can be epoxidized in the absence of a solvent by trimethylsulfonium iodide or trimethylsulfoxonium iodide and potassium fluoride/aluminum oxide.
Because it is difficult to achieve a sufficiently high yield by these conventionally known methods and, further, because these methods require complicated procedures, the present inventors contemplated improvement of the process for the preparation of azolylmethylcycloalkanol derivatives represented by formula (I), which is hereinafter described.
The present inventors have undertaken extensive studies in order to achieve this objective and found that the target compound can be produced at a high yield by carrying out a series of reactions in the preparation of the aforementioned compound (A), including an S-methylide preparation step, an epoxidation step, and an azolation step, in an organic solvent, in the presence of a metal oxide, and in the solid-liquid two-phase reaction system. This finding has led to the completion of the present invention.